Excitation of indole analogs by phagocytosing leukocytes

The system suspended with phagocytosing leukocytes and related system produce weak light which could be greatly amplified by indole analogs with plain fatty acids at 3 position. Main emitting species in indole-3-acetic acid or indole-3-propionic acid-sensitized system was analyzed spectrometrically in the dark and ascribed to the transition of an excited indole compound in triplet state to its ground state. Such an excited species would be generated by the oxidative way of the indole analogs but not through the dioxetane structure of 2 and 3 positions on indole ring.     

Papillary projections at the lingual margin in the striped dolphin,Stenella coeruleoalba,with Special Reference to Their Development and Regression

Papillary projections along the anterolateral margin of the tongue were observed in fetal and young stages of the striped dolphin, Stenella coeruleoalba. Papillary projections appear in the prenatal period and attain maximum development in the early postnatal period. They almost disappear by weaning. Vestigial eminences remain at the corresponding region, but they completely disappear in the adult. The papillary projections observed differ markedly from the lingual papillae of the general mammalian tongue as they are temporary, localized at the anterolateral margin and large in size. The projections were also present in young individuals of some other dolphins. No taste buds could be seen on the projections in any of the stages of all specimens observed. Such projections may have important mechanical functions during suckling in these mammals.     

Effects of temperature and light on cyst germination and germinated cell survival of the noxious raphidophyte Heterosigma akashiwo

The effects of temperature and light on the germination of Heterosigma akashiwo cysts were examined using bottom sediments collected from Hakata Bay, Japan. In a suspension of mixed sediment and seawater in the temperature range of 5–30 °C, motile cells emerged within 3 weeks, but at ≤12 °C the cell numbers were markedly lower and the emergence of motile cells delayed. When suspension samples incubated at various temperatures were moved to 20 °C and incubated, only a few additional motile cells emerged. The number of motile cells germinated in the dark was significantly lower than under light conditions. When suspension samples incubated in the dark were exposed to light, only a few additional motile cells emerged. These results indicate that the initiation of germination in Heterosigma cysts suspended in seawater is not dependent on temperature and light conditions, although the speed of the germination process is affected by temperature, and cell survival just after germination is strongly affected by temperature and light.     

Analysis of a lottery competition model with limited nutrient availability

How a plant species utilizes a limited nutrient is important for its survival. The purpose of this work is to examine how nutrient utilization mechanisms (for seed production) affect the coexistence of competing plant species. We construct a revised lottery model that uses one of three possible kinds of nutrient utilization functions. In all cases the models suggest that two species can coexist under certain circumstances, but that three species cannot coexist, at least when the nutrient utilization functions are continuous functions of nutrient uptake. However, in the discontinuous case three species can coexist in a state of sustained oscillations. The results suggest that one need pay close attention to the differences in the nutrient utilization mechanisms among competing plant species in order to ascertain the competitive outcome.     

Chronic mucocutaneous candidiasis caused by a gain-of-function mutation in the STAT1 DNA-binding domain

Chronic mucocutaneous candidiasis (CMC) is a heterogeneous group of primary immunodeficiency diseases characterized by chronic and recurrent Candida infections of the skin, nails, and oropharynx. Gain-of-function mutations in STAT1 were very recently shown to be responsible for autosomal-dominant or sporadic cases of CMC. The reported mutations have been exclusively localized in the coiled-coil domain, resulting in impaired dephosphorylation of STAT1. However, recent crystallographic analysis and direct mutagenesis experiments indicate that mutations affecting the DNA-binding domain of STAT1 could also lead to persistent phosphorylation of STAT1. To our knowledge, this study shows for the first time that a DNA-binding domain mutation of c.1153C>T in exon 14 (p.T385M) is the genetic cause of sporadic CMC in two unrelated Japanese patients. The underlying mechanisms involve a gain of STAT1 function due to impaired dephosphorylation as observed in the coiled-coil domain mutations.     

Mitochondrial P5, a member of protein disulphide isomerase family, suppresses oxidative stress-induced cell death

P5, one of the protein disulphide isomerase (PDI) family members, catalyses disulphide bond formation in proteins and exhibits molecular chaperone and calcium binding activities in vitro, whereas its physiological significance remains controversial. Recently, we have reported that P5 localizes not only in the ER but also in mitochondria, although it remains unclear so far about its physiological significance(s) of its dual localization. Here we report that H(2)O(2)- or rotenone-induced cell death is suppressed in MTS-P5 cells, which stably express P5 in mitochondria. H(2)O(2)-induced cell death in Saos-2 cells occurred, in large part, through caspase-independent and poly(ADP-ribose) polymerase (PARP)-dependent manner. In MTS-P5 cells challenged with H(2)O(2) treatment, PARP was still activated, whereas release of cytochrome c or apoptosis-inducing factor and intramitochondrial superoxide generation were suppressed. We also found that mitochondrial P5 was in close contact with citrate synthase and maintained large parts of its activity under H(2)O(2) exposure. These results suggest that mitochondrial P5 may upregulate tricarboxylic acid cycle and possibly, other intramitochondrial metabolism.     

Synthesis and structure-activity relationship of 4-amino-2-phenylpyrimidine derivatives as a series of novel GPR119 agonists

Through preparation and examination of a series of novel 4-amino-2-phenylpyrimidine derivatives as agonists for GPR119, we identified 2-(4-bromophenyl)-6-methyl-N-[2-(1-oxidopyridin-3-yl)ethyl]pyrimidin-4-amine (9t). Compound 9t improved glucose tolerance in mice following oral administration and showed good pharmacokinetic profiles in rats.